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Title: Selective destruction of cells infected with human immunodeficiency virus

Abstract

Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a variant of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

Inventors:
;
Publication Date:
Research Org.:
Idaho National Laboratory (INL), Idaho Falls, ID (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1174512
Patent Number(s):
6,627,197
Application Number:
09/785,921
Assignee:
Bechtel BWXT Idaho, LLC (Idaho Falls, ID)
DOE Contract Number:  
AC07-94ID13223
Resource Type:
Patent
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Keener, William K., and Ward, Thomas E. Selective destruction of cells infected with human immunodeficiency virus. United States: N. p., 2003. Web.
Keener, William K., & Ward, Thomas E. Selective destruction of cells infected with human immunodeficiency virus. United States.
Keener, William K., and Ward, Thomas E. 2003. "Selective destruction of cells infected with human immunodeficiency virus". United States. https://www.osti.gov/servlets/purl/1174512.
@article{osti_1174512,
title = {Selective destruction of cells infected with human immunodeficiency virus},
author = {Keener, William K. and Ward, Thomas E.},
abstractNote = {Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a variant of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.},
doi = {},
url = {https://www.osti.gov/biblio/1174512}, journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Sep 30 00:00:00 EDT 2003},
month = {Tue Sep 30 00:00:00 EDT 2003}
}

Works referenced in this record:

Ricin: structure, mode of action, and some current applications.
journal, February 1994


Preparation and characterization of recombinant proricin containing an alternative protease-sensitive linker sequence
journal, September 1992


Rationale for the Use of Immunotoxins in the Treatment of HIV-infected Humans
journal, January 1998


Bryodin, a single-chain ribosome-inactivating protein, selectively inhibits the growth of HIV-1-infected cells and reduces HIV-1 production
journal, December 1993


HIV-infected cells are killed by rCD4-ricin A chain
journal, November 1988


Recombinant proricin binds galactose but does not depurinate 28 S ribosomal RNA
journal, September 1989


Human Immunodeficiency Virus Protease Inhibitors
journal, June 1997